Predictive value of pre-procedural mitral regurgitation on 1

Predictive Value of Pre-procedural Mitral

Regurgitation on 1-Year Mortality in

Patients undergoing a TAVI procedure:

Insights from the FRANCE2 Registry

E Van Belle, E Teiger, F Juthier, H Eltchaninoff, A

Leguerrier, P Leprince, M Laskar, M Gilard, B Iung,

and A Prat, for the FRANCE2 Registry Investigators

Conflict of interest

• None

Background

• The presence of a mitral regurgitation (MR) is

known as an independent predictor of poor

clinical outcome in patients undergoing

conventional aortic valve replacement for aortic

stenosis.

• The predictive value of pre-procedural MR on

clinical outcome after transcatheter aortic valve

implantation (TAVI) is unknown.

Mortality according to the presence

of MR in the PARTNER trial

25% of the population had moderate (to severe) MR

PARTNER A

PARTNER B

20% of the population had moderate (to severe) MR

MR and TAVI: PARTNER Insights

• 20-25% of the patients included had a moderate (to severe) mitral regurgitation.

• In patients with moderate to severe MR, 1 year mortality was 23-25%.

• The presence of a preprocedural MR was not associated with an increased mortality rate (compared to patients without MR).

• But: – Selected populations

– Small number of patients with MR (n=38+66=104)

– Only one type of device used

Methods

• 3195 consecutive patients were enrolled between January 2010 and October 2011 in 33 French centers and included in the FRANCE 2 Registry.

• MR was graded according to pre-procedural transthoracic echocardiography (TTE) as none/trivial (=0), mild (=1), moderate (=2), moderate-to-severe (=3), or severe (=4).

• Clinical Follow-up was obtained in all patients at 302 days ±164 days

Baseline Characteristics N=3,195

Age, years 83±7

Male, n 1630 (51)

Logistique Euroscore 21.9±14.3

STS Score 14.4±11.9

BMI, kg/m2 26.1±4.9

Diabetes mellitus, n 797(24.9)

NYHA 2.88±0.64

Coronary artery disease, n 1493 (46.7)

Previous MI 502 (16.2)

Previous cardiac surgery 668 (21.1)

Atrial fibrillation, n 820(25.7)

COPD 748 (23)

Baseline Characteristics

N=3,195

Pre-prodecural TTE

Aortic valve area (mm) 0.67±0.18

Mean Aortic gradient (mmHg) 48.1±16.5

Aortic Annulus diameter 22.1±2.1

AR grade ≥2,n 539(16.9)

LVEF, % 53.3±14.1

PAPs, mmHg 45.5±14.1

No MR, n

MR grade =1, n

MR grade = 2, n

MR grade = 3 or 4, n

1183(37.0)

1351(42.3)

603(18.9)

58 (1.8)

Procedural Characteristics

N=3,195

Delivery approach

Femoral

Apical

Other

74.0%

17.6%

8.4%

Valve type

Balloon-Expendable

Self-Expendable

2122 (66.9)

1049 (33.1)

Valve size

Balloon-Expendable 23 mm



28.6%

35.9%

2.4%

Self-Expendable 26 mm



11.5%

21.2%

0.4%

1 year Actuarial mortality according to

pre-procedural mitral regurgitation

MR grade ≥ 2

MR grade = 1

MR grade = 0

0 50 100 150 200 250 300 350

Days

75

80

85

90

95

100

Su

rviv

al,

%

p=0.003

25% mortality

Correlates of Mitral Regurgitation:

A multivariate analysis

Beta 95% CI Beta P

Euroscore, 5% increase + 0.03 0.02-0.04 0.0001

LV ejection fraction, 5%

decrease

+ 0.02 0.01-0.03 0.0001

Female gender + 0.11 0.05-0.16 0.0001

Body mass index (-) 0.01 (-)0.02 – (-)0.01 0.0002

Atrial Fibrillation + 0.10 0.04-0.16 0.001

NYHA + 0.07 0.03-0.11 0.001

Other parameters in the model are : Age, diabetes mellitus, history of MI, history of peripheral arterial disease, COPD, PAPs, Severity of CAD and renal failure,

Predictors of 1-year mortality:

A multivariate analysis (incl. Euroscore)

Chi 2 Hazard

Ratio

95% CI HR P

Euroscore, 5% increase 26.7 1.09 1.05-1.12 0.0001

Atrial Fibrillation 18.3 1.50 1.24-1.80 0.0001

Non-femoral approach 15.5 1.62 1.27-2.05 0.0001

NYHA (one class increase) 14.3 1.32 1.14-1.53 0.0002

Body mass index 8.6 0.97 0.95-0.99 0.003

Preproc. Mitral Regurgitaion

- Grade 1

- ≥Grade 2

2.1 -

1.16

1.09

-

0.94-1.42

0.85-1.40

0.39

Self-expendable device 1.6 1.15 0.93-1.40 0.19

Other parameters in the model are : gender, Diabetes mellitus, history of MI, history of peripheral arterial disease, and Severity of CAD.


A multivariate analysis (non incl. Euroscore)

Chi 2 Hazard

Ratio

95% CI HR P

Renal failure 37.9 2.08 1.65-2.64 0.0001

Age, 5 year increase 8.2 1.10 1.03-1.18 0.004

LV ejection fraction, 5% decrease 6.3 1.04 1.01-1.08 0.01




Body mass index 8.8 0.97 0.95-0.98 0.003


- Grade 1

- ≥Grade 2

2.4 -

1.18

1.13

-

0.96-1.45

0.88-1.45

0.29


Other parameters in the model are : individual Euroscore parameters, gender, Diabetes mellitus, history of MI, history of peripheral arterial disease, and Severity of CAD.

Mortality according to pre-procedural

mitral regurgitation in patients treated

with a Balloon-expendable device

MR grade ≥ 2

MR grade = 1

MR grade = 0

25% mortality

0 50 100 150 200 250 300 350

Days

75

80

85

90

95

100

Su

rviv

al,

%

20% mortality

Mortality according to pre-procedural

mitral regurgitation in patients treated

with a Self-expendable device

MR grade ≥ 2

MR grade = 1

MR grade = 0

25% mortality

0 50 100 150 200 250 300 350

Days

75

80

85

90

95

100

Su

rviv

al,

%

20% mortality

Temps

Summary

• In a population of > 3,000 consecutive TAVI patients, the presence of moderate (to severe) MR is observed in 21% of the cases.

• By univariate analysis, the presence of a mild (grade1) or a moderate (grade 2) MR is associated with a higher 1-year mortality after TAVI.

• However, since pre-procedural MR is associated with important risk markers such as atrial fibrillation, a lower BMI, a higher NYHA class or a higher logistic Euroscore; pre-procedural MR is not an independent predictor of 1 year mortality.

• Mortality in patients with a moderate (to severe) MR remains below 25% at one year.

• In patients with MR, mortality is not modified by the type of device (BE vs SE) to be used.

Clinical implications

These findings suggest that, in itself, the

presence of a mild or a moderate MR

should not refrain from performing TAVI

and should not impact the type of device

to be used.

Predictors of Mitral Regurgitation

≥Grade 2 : A multivariate analysis

Hazard

Ratio

95% CI P

Male gender 1.78 1.35-2.38 0.0001

Diabetes Mellitus 0.73 0.56-0.97 0.02

Mitral Regurgitation at baseline 1.33 1.04-1.70 0.02

Aortic Regurgitation at baseline 1.29 1.01-1.68 0.04

Aortic Annulus diameter (mm,

TTE)

1.09 1.02-1.16 0.01

Atrial Fibrillation 1.20 0.96-1.51 0.11

Self-Expendable Device 2.04 1.43-2.91 0.0001

femoral approach 2.25 1.33-3.82 0.002

Prosthesis diameter (3 mm

incr.)

0.69 0.51-0.92 0.01 Other parameters in the model are : Age, Euroscore, BMI, LV ejection fraction, Atrial Fibrillation.



Hazard

Ratio

95% CI P

Male gender 1.78 1.35-2.38 0.0001





TTE)

1.09 1.02-1.16 0.01





incr.)




Hazard

Ratio

95% CI P

Male gender 1.78 1.35-2.38 0.0001





TTE)

1.09 1.02-1.16 0.01





incr.)




Hazard

Ratio

95% CI P

Male gender 1.78 1.35-2.38 0.0001





TTE)

1.09 1.02-1.16 0.01





incr.)



A multivariate analysis (with Euroscore)

Chi 2 Hazard

Ratio

95% CI HR P


- Gradre 1

- ≥Grade 2

2.1 -

1.16

1.11

-

0.94-1.43

0.87-1.43

0.35


Renal failure 22.0 1.81 1.41-2.32 0.0001






Other parameters in the model are : gender, Diabetes mellitus, history of MI, history of peripheral arterial disease, and Severity of CAD.

Summary (2)

• The clinical significance (mortality) of an AR

grade ≥2 was the same for Balloon-expendable

and self-expendable devices (HR≈2-2.50).

• The clinical significance (mortality) of an AR

grade ≥2 was higher for non-femoral than for

femoral approaches (HH ≈4.0 vs 2.0).

• Annulus diameter and prosthesis diameter are 2

major determinants of AR for Balloon-

expendable devices.

• Annulus diameter and prosthesis diameter are

not determinants of AR for Self-expendable

devices.


A multivariate analysis

Predictors of 1-year Mortality : a multivariate analysis

0.1 1 10

Female Gender

Apical Approach

NYHA (one class increase)

Renal Failure

Atrial Fibrillation

grade 2)Peri-valvular AR (

p

0.0001

0.0001

0.001

0.007

0.04

0.03

Hazard Ratio (95% CI)

Other parameters in the model are : Valve type, individual Euroscore parameters, age, Diabetes mellitus, history of MI, history of peripheral arterial disease, Severity of CA Dand LV ejection fraction.

Predictors of Peri-valvular AR ( grade 2): a multivariate analysis

0.1 1 10

mm increase)Prosthesis

Femoral Approach

Self Expendable Device

Atrial Fibrillation

mm, TTE)Aortic Annulus

AR at baseline

MR at baseline

Diabetes Mellitus

Male Gender

p

0.0001

0.02

0.04

0.11

0.002

0.01

0.02

0.01

0.0001

Odds ratio

Predictors of Perivalvular Aortic Regurgitation


Other parameters in the model are : Age, Euroscore, BMI, LV ejection fraction, Atrial Fibrillation.

21,9

10,7

13,9

8

0

5

10

15

20

25

Self-

expend.-

femoral

Self-

expend.-

non-femoral

Balloon-

Expend.-

Femoral

Balloon-

Expend.-

non-Femoral

Grade ≥2

Perivalvular regurgitation ≥ grade 2

according to device and approach

N=731 (81%)

N=166 (19%)

N=1354 (72%)

N=518 (28%)

%

15,6

21,8

33,3

12,6 12

5

0

5

10

15

20

25

30

35

26 29 31 23 26 29

Grade ≥2

Perivalvular regurgitation ≥ grade 2

according to device diameter and type

Self-expendable device Balloon-expendable device

%

9,48

22,920,7

1921,1

18,2

11,3

0

5

10

15

20

25

30

<10 10 to 15 15 to 20 > 20

Balloon-Expendable

Self-expendable

Perivalvular regurgitation ≥ grade 2 according to

cover index and device

%

Impact of perivalvular regurgitation on 1

year mortality according to valve type

Su

rviv

al, %

Days

AR grade ≥ 2

HR=2.68

AR grade = 0 or 1

Balloon Expendable

AR grade = 0 or 1

Self Expendable

AR grade ≥ 2

HR=2.10

,6

,65

,7

,75

,8

,85

,9

,95

1

0 50 100 150 200 250 300 350

Impact of perivalvular regurgitation on 1 year

mortality according to delivery approach

Su

rviv

al,

%

Days

50

60

70

80

90

100

0 50 100 150 200 250 300 350

AR grade ≥ 2

HR=2.06

AR grade = 0 or 1

Femoral

AR grade = 0 or 1

Non-Femoral

AR grade ≥ 2

HR=3.80

Predictors of Perivalvular Aortic Regurgitation≥Grade 2 :

Balloon Expendable device (multivariate analysis)

Predictors of Peri-valvular AR ( grade 2): Balloon Expendable Device

0.1 1 10

mm increase)Prosthesis

Femoral Approach

Atrial Fibrillation


AR at baseline

MR at baseline

Diabetes Mellitus

Male Gender

p

0.0002

0.004

0.11

0.05

0.0001

0.15

0.0004

0.01

Odds ratio

Other parameters in the model are : Age, Euroscore, BMI, LV ejection fraction.

Predictors of Perivalvular Aortic Regurgitation ≥Grade 2:

Self Expendable device (multivariate analysis)

Predictors of Peri-valvular AR ( grade 2): Self Expendable Device

0.1 1 10

3 mm increase)Prosthesis

Femoral Approach

Atrial Fibrillation


AR at baseline

MR at baseline

Diabetes Mellitus

Male Gender

p

0.08

0.82

0.19

0.83

0.60

0.06

0.89

0.009

Odds ratio

Other parameters in the model are : Age, Euroscore, BMI, LV ejection fraction.

Documents

Predictive value of pre-procedural mitral regurgitation on 1